Low immunogenicity of LNP allows repeated administrations of CRISPR-Cas9 mRNA into skeletal muscle in mice
| Autor: | Kenjo, Eriya, Hozumi, Hiroyuki, Makita, Yukimasa, Iwabuchi, Kumiko A., Fujimoto, Naoko, Matsumoto, Satoru, Kimura, Maya, Amano, Yuichiro, Ifuku, Masataka, Naoe, Youichi, Inukai, Naoto, Hotta, Akitsu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Gene Editing
Multidisciplinary Science General Physics and Astronomy Exons Genetic Therapy Neuromuscular Diseases General Chemistry Neuromuscular disease Article General Biochemistry Genetics and Molecular Biology Dystrophin Muscular Dystrophy Duchenne Disease Models Animal Mice Targeted gene repair CRISPR-Associated Protein 9 Liposomes Animals Humans Nanoparticles RNA Messenger CRISPR-Cas Systems Muscle Skeletal |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Genome editing therapy for Duchenne muscular dystrophy (DMD) holds great promise, however, one major obstacle is delivery of the CRISPR-Cas9/sgRNA system to skeletal muscle tissues. In general, AAV vectors are used for in vivo delivery, but AAV injections cannot be repeated because of neutralization antibodies. Here we report a chemically defined lipid nanoparticle (LNP) system which is able to deliver Cas9 mRNA and sgRNA into skeletal muscle by repeated intramuscular injections. Although the expressions of Cas9 protein and sgRNA were transient, our LNP system could induce stable genomic exon skipping and restore dystrophin protein in a DMD mouse model that harbors a humanized exon sequence. Furthermore, administration of our LNP via limb perfusion method enables to target multiple muscle groups. The repeated administration and low immunogenicity of our LNP system are promising features for a delivery vehicle of CRISPR-Cas9 to treat skeletal muscle disorders. 筋ジストロフィーのゲノム編集治療を目指したLNP-mRNA輸送システムの開発. 京都大学プレスリリース. 2021-12-08. Nanotechnology for genome editing in multiple muscles simultaneously. 京都大学プレスリリース. 2021-12-08. |
| Databáze: | OpenAIRE |
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